Long‐term Follow‐up of Low‐dose External Pituitary Irradiation for Cushing's Disease

Abstract

Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. Two of these received no further active treatment, one underwent successful pituitary surgery, one underwent a second course of low-dose external irradiation (as yet unsuccessful) and one has been treated with metyrapone for a total of 75 months. One of the 13 patients who did not respond received a further course of low-dose pituitary irradiation with prompt remission and two have received metyrapone for 41 months and 15 years without ill effect. One patient died from cerebrovascular disease. The remaining nine patients underwent bilateral adrenalectomy (one after unsuccessful pituitary surgery) with rapid resolution of hypercortisolism. Five of these patients have developed hyperpigmentation and elevated ACTH levels (range 505-1150 ng/l). A pituitary microadenoma has been demonstrated on CT scan in three and successfully removed by microadenomectomy. In the present series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy.

THERAPY OF ENDOCRINE DISEASE: Steroidogenesis enzyme inhibitors in Cushing's syndrome

“…Prolonged administration of either metyrapone or KTZ appears safe and should be considered in cases where other options (surgery or radiotherapy) have been exhausted or where there is a strong patient preference for a non-surgical approach (115). The efficacy of medical therapy appears to be better in long-term treated groups and this may be associated with the fact that most patients by that stage have undergone other therapies that have reduced the disease burden.…”

Tratamento medicamentoso dos tumores hipofisários. parte II: adenomas secretores de ACTH, TSH e adenomas clinicamente não-funcionantes

“…Além disso, podem ser necessários até 2 anos ou mais para que se obtenha um efeito terapêutico pleno (5,(13)(14)(15)(16). Um outro importante inconveniente da radioterapia é o freqüente surgimento de hipopituitarismo (1,2).…”

“…Um outro importante inconveniente da radioterapia é o freqüente surgimento de hipopituitarismo (1,2). Entre 139 pacientes com doença de Cushing, observaram-se as seguintes deficiências hormonais: GH em 86%, ACTH em 20%, LH/FSH em 18% e TSH em 6% (13)(14)(15)(16). A principal indicação da radioterapia é para pacientes com hipercortisolismo persistente ou recidivante após a TSA (2,5); nesses casos, consegue-se uma taxa de remissão de 55 a 83%, geralmente dentro dos primeiros dois anos após a radioterapia (17,18).…”

Radiotherapy and radiosurgery for Cushing's disease

“…Following conventional fractionated RT of ACTH secreting pituitary adenoma the reported tumour and hormone control at a median follow up of 8 years are 97% and 74% (table 1) (2,(7)(8)(9)(10)(11)(12). Urinary free cortisol (UFC) is reduced to 50% of pre-treatment value in 6-12 months (10,12) and plasma cortisol in 12 months (12).…”

“…This leads not only to lower remission rates but is also associated with a higher risk of biochemical recurrence (7)(8)(9).…”